HMG-CoA reductase inhibitors, such as rosuvastatin calcium, fluvastatin sodium, pitavastatin calcium, are known as a drug useful for reducing LDL-cholesterol and triglyceride level (for example, EP0521471, U.S. Pat. No. 5,354,772, EP 0304063, and etc). The chemical name of rosuvastatin calcium is E-7-[2-(N-methyl-N-methanesulfonylamino)-4-(4-fluorophenyl)-6-isopropyl-pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxyhept-6-enoic acid 1/2 calcium salt. The chemical name of fluvastatin sodium is (3R,5S,6E)-7-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-3,5-dihydroxy hept-6-enoic acid sodium salt. The chemical name of pitavastatin calcium is (3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy hept-6-enoic acid 1/2 calcium salt. They have the following chemical structures of Formula 1a (rosuvastatin calcium), Formula 1b (fluvastatin sodium), and Formula 1c (pitavastatin calcium), respectively.

For example, a process for preparing rosuvastatin or its salt has been disclosed in EP0521471. The process described in EP0521471 involves preparing an ester-bond-containing compound through Wittig Reaction and preparing a dihydroxy-group-containing intermediate under reduction condition using very low temperature. And also, the process involves preparing rosuvastatin sodium salt through hydrolysis of the dihydroxy-group-containing intermediate, converting the sodium salt to its calcium salt. In the process, both the ester-bond-containing compound and the dihydroxy-group-containing intermediate have liquidic forms and require purifying with silica gel column chromatography, in order to remove impurities derived from the reactions, which makes the process not suitable for industrial mass production. Because the reduction for preparing the dihydroxy-group-containing intermediate should be performed under very low temperature condition and also requires using diethylmethoxyborane and sodium borohydride which are very explosive and toxic, it is difficult to apply the process to industrial mass production.
As an improved process for preparing rosuvastatin calcium, WO 2000/049014 has disclosed a process involving preparing a t-butyl ester bond-containing compound via Horner-Emmons Reaction; deprotecting the protecting group under acidic condition to obtain a diol-containing intermediate; hydrolyzing the intermediate under basic condition to obtain rosuvastatin sodium salt; purifying the sodium salt by converting to rosuvastatin methylamine salt followed by filtering; and converting to rosuvastatin calcium. And also, WO 2008/044243 has disclosed a process for preparing rosuvastatin calcium, using an amide-bond-containing compound having alkyl-substituted amine moiety, instead of the t-butyl ester bond-containing compound.
Meanwhile, WO 2005/042522 has disclosed a process for preparing rosuvastatin calcium via a lactone ring-containing intermediate from an ester bond-containing compound. However, in order to prepare the lactone ring-containing intermediate from an ester bond-containing compound according to WO 2005/042522, the process requires (1) hydrolyzing under acidic condition to deprotect the hydroxyl-protecting group, (2) rehydrolyzing under alkaline condition (e.g., sodium hydroxide used) to hydrolyze the ester-bond, and (3) cyclizing under acidic condition using severe condition (i.e., at 105° C.). Therefore, for preparing the lactone ring-containing intermediate, it is necessary to perform multiple steps, including cyclization under severe condition, which makes the process not suitable for industrial mass production.